Dr. Steven Almo, an x-ray crystallographer with significant synchrotron experience, has spearheaded a collaborative effort in conjunction with Dr. Zhong-Yin Zhang, an enzymologist, and Dr. David Lawrence, a synthetic chemist. The goal of this project is the structure-based design of potential therapeutic agents which bind to protein tyrosine phosphatases (PTPases), and the elucidation of the structures of novel PTPases. Since data collected on rotating anode sources at AECOM were of insufficient resolution, single-crystal diffraction data collected at beamline X9B has been absolutely essential for current progress. H Using synchrotron methods, Dr. Almo's group has solved the Hstructure of human protein tyrosine phosphatase 1B (PTP1B) in complex Hwith several different substrates, using 1.9A data collected at X9B. HThe complex of PTP1B and a synthetic high-affinity non-peptide Hsubstrate synthesized by the Lawrence group has demonstrated the Hexistence of a novel aryl phosphate binding site, which provides a new Hparadigm for the design of tight-binding inhibitors. This is the Hhighest resolution reported for this enzyme and this work has recently Hled to a publication in PNAS. Based on these findings, the Lawrence Hlab has synthesized a series second generation of PTP1B ligands that Hencompass both aryl phosphate functionalities and data has been Hcollected at X-9B on several different complexes.